Presence Of Azotemia Research Articles

C4 uremic variant: an acquired C4 allotype.

The major histocompatibility complex (MHC)-linked complotype region includes alleles for B, C2, and C4 loci. These loci are closely linked to each other and to HLA-DR on chromosome 6. The duplicated C4 loci, C4A and B, are especially polymorphic. In seven patients with renal insufficiency, we observed a C4 variant with electrophoretic mobility between C4B2 and C4B3. Four of these patients were detected during a study of MHC markers in membranoproliferative glomerulonephritis. Complete complotype and HLA data from families of five of the seven patients demonstrated that the variant was not inherited. The pattern was revealed by immunofixation electrophoresis and also by C4-specific hemolytic overlay. In serial plasma specimens taken from one patient, the C4 variant appeared only after the patient became uremic. However, the variant could not be produced in normal plasma after incubation with C4-depleted uremic plasma. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions of immunoprecipitated C4 from these patients showed C4A and C4B alpha chains of normal molecular mass; incompletely processed forms of C4 were not observed. We believe that this variant is probably acquired in the presence of uremia and may represent the C4B2.9 allele found by Wank and co-workers in many patients with glomerulonephritis. Family studies are mandatory to distinguish genetic variants from acquired alterations in the C4 phenotype.

Intraarterial digital subtraction angiography in hypertensive azotemic patients.

Ten intraarterial digital subtraction angiography studies in nine azotemic patients were reviewed to assess the technical adequacy and the effect of contrast load on renal function. All studies were of diagnostic quality. In only two of 10 studies was there a mild transient deterioration in the degree of renal insufficiency. Intraarterial digital subtraction angiography is a reliable method that can be used to evaluate the renal arteries, even in the presence of azotemia.

Precocious Puberty and Chronic Renal Failure

• A 7½-year-old boy with chronic renal failure (CRF) experienced transient central isosexual precocious puberty. Simultaneously, he demonstrated hyperprolactinemia with galactorrhea and apparent secondary or tertiary hypothyroidism. These findings could have been a consequence of an unexplained hypothalamic dysregulation. During this period, marked linear growth ensued (8.7 cm during nine months) associated with rapid bone age advancement (four years during a 21-month period). Whereas most boys with CRF demonstrate delayed pubertal development and suppressed linear growth, our patient's transient condition demonstrated that both growth and puberty can occur in the presence of uremia. ( Am J Dis Child 1983;137:956-958)

Nonoliguric Acute Renal Failure in the Newborn

Fifteen newborn babies with azotemia without oliguria were studied. Group A infants had increased BUN levels and decreased creatinine clearance (Ccr) for gestational and postnatal age, and were compared with group B infants, who had increased BUN levels and normal Ccr. The Ccr was 0.35 mL/min in group A and 0.76 mL/min in group B. Urine volume during the same period was 2.45 mL/kg/hr in group A and 4.66 mL/kg/hr in group B. No significant differences in fractional sodium excretion; urine to plasma ratios of creatinine, osmolality, and sodium; and renal failure index were present between the two groups. The results suggest that nonoliguric acute renal failure is a diagnostic entity in the newborn. The Ccr is the most useful indicator for defining renal function in the presence of azotemia and normal urine volume.

Hypercalcemia in patients with squamous cell carcinoma of the cervix

Hypercalcemia was identified in approximately 1% of the patients with epidermoid cervical cancer admitted to the gynecologic oncology service at LAC/USC Women's Hospital over a 6.5-year period. Nonspecific neurologic manifestations of weakness, obtundation, and coma were the predominant presenting features. The response to anticalcemic therapy depended upon the extent of the underlying malignancy and the presence of uremia. The appearance of hypercalcemia in these patients usually signified a rapidly deteriorating clinical course which was irreversible despite aggressive medical management in some instances. Recent concepts in the humoral mechanisms of cancer related hypercalcemia, briefly reviewed here, may provide safer and more successful avenues of treatment for salvageable patients in the near future.

On the influence of extracellular fluid volume expansion and of uremia on bicarbonate reabsorption in man.

The patterns of bicarbonate reabsorption during increasing plasma concentrations were studied in subjects with a range of glomerular filtration rates (GFR) from 170 to 2 ml/min. In a group of five subjects with GFR values above 30 ml/min, paired bicarbonate titration studies were performed first under conditions which minimized extracellular fluid (ECF) volume expansion, and second under conditions which were conducive to exaggerated expansion of ECF volume. In patients with GFR values below 30 ml/min, a single protocol was employed. Studies also were performed on two patients with far advanced renal disease who were nephrotic and exhibited a sodium-retaining state. When ECF volume expansion was minimized in the nonuremic subjects, values for bicarbonate reabsorption were well in excess of the usually accepted Tm level and over the range of plasma bicarbonate concentrations employed, no evidence of a Tm phenomenon was observed. A similar pattern emerged in the two nephrotic patients despite the presence of uremia. However, with both exaggerated expansion of ECF volume (GFR greater than 30) and in patients with advanced renal disease in the absence of exaggerated ECF volume expansion a tendency towards saturation kinetics for bicarbonate reabsorption was demonstrable. In comparing the minimized with the exaggerated expansion studies, evidence emerged for a decrease in both bicarbonate reabsorption per unit of GFR and the absolute rate of bicarbonate reabsorption. When ECF volume expansion was exaggerated in uremic patients after stable rates of bicarbonate reabsorption had been achieved, a decrease in reabsorption per unit of GFR and in absolute bicarbonate reabsorption occurred. The possible relationship of the factors controlling sodium excretion to the observed patterns of bicarbonate reabsorption is considered in the text.

Hazards of Ethacrynic Acid

To the Editor.— I agree that in a patient who may already have volume depletion additional fluid depletion following the administration of a diuretic may further compromise the marginally functional kidneys. However, in my communication I pointed out that obviously adequate hydration should be first achieved. In addition to this, if one is using a so-called loop diuretic to determine whether or not the oliguria would respond, I am sure that careful observation of the urine volume would be in order for this reason, and thus, it is highly unlikely that the patients would have fluid depletion before adequate replenishment could be given. I agree that the possibility of deafness associated with ethacrynic acid and the presence of azotemia is a potential hazard. However, in using this technique for more than three years, we have seen only three cases of transient deafness and never one of permanent deafness. In the

Hazards of Ethacrynic Acid

To the Editor.— In the review article entitled Acute Renal Failure by Merrill (211:289, 1970), it is recommended that a test dose of ethacrynic acid as high as 200 mg be given to assist in determining the existence of prerenal failure. I feel that this procedure carries certain definite hazards. First, in a patient who may already have a volume depletion, additional fluid depletion after the administration of this highly potent diuretic may further compromise the marginally functional kidneys. Second, there are now a number of reported cases of both transient and possibly permanent deafness associated with the use of this diuretic in the presence of azotemia (Lancet1:41, 1969; Lancet1:77, 1969; andArch Intern Med11:715, 1966). Unless there are adequate data substantiating the value of the procedure, it is my feeling that the risks definitely outweigh the benefits of this therapeutic maneuver.

Ototoxicity of ethacrynic acid and aminoglycoside antibiotics in uremia.

THE ototoxic effects of aminoglycosides such as streptomycin, kanamycin and neomycin are well established. Since renal failure increases the hazard of ototoxicity from these drugs, it can be expected that, in the presence of azotemia and delayed drug excretion, other agents thought to be minimally ototoxic may exhibit an enhanced capacity for this adverse effect.1 Before the report of Schneider and Becker2 ethacrynic acid was not considered an ototoxic drug. They described the induction of acute transient hearing loss by ethacrynic acid in five patients with marked impairment of renal function.Others3 4 5 6 have alluded to single cases of similar effects. . . .

Gastric secretory studies in patients undergoing chronic hemodialysis.

The composition of gastric secretion in the presence of azotemia has been well defined. The composition of gastric secretion in patients undergoing chronic hemodialysis has not been previously studied. Several reports emanating from dialysis centers in both the United States and England suggest that peptic ulceration may occur more frequently in patients undergoing chronic hemodialysis than in the general population. To better understand the etiology of peptic disease and the possible relationship existing between it and gastric secretion in a chronically hemodialyzed population, gastric secretory studies were performed in a series of 11 patients. The results of these studies indicate basal hyposecretion and hypoacidity to be the most characteristic feature of this group. Following maximal Histalog stimulation, patients were able to secrete a normal amount of gastric juice with a normal pH. Of the patients studied, only one, who manifested basal hyperacidity, had peptic disease. Correlation between volume and acidity of gastric juice and age, duration and type of disease, and biochemical abnormalities could not be demonstrated. It is concluded that factors other than gastric acidity must be implicated in peptic disease occurring in a chronically hemodialyzed population.

Renin and angiotensin II studies in malignant hypertension after x-irradiation for seminoma.

A case of malignant hypertension after X-irradiation of an abdominal malignancy is presented. Renal and serum renin levels were elevated consistent with the renal origin of this type of hypertension. The patient showed diminished responsiveness to angiotensin II. Despite the presence of azotemia and evidence of bilateral disease, unilateral nephrectomy of the nonfunctioning right kidney led to reversal of the hypertensive process and a fall in serum renin levels to normal.

The role of the kidney in the catabolism of Bence Jones proteins and immunoglobulin fragments.

The role of the kidney in the catabolism of Bence Jones proteins, intact IgG molecules, and isolated L chains, Fab and Fc fragments of IgG, was studied. The proteins were purified, radioiodinated, and their survival times measured in nephrectomized, ureter-severed, and control mice. Active endogenous catabolism was the major factor in overall Bence Jones metabolism since excretion as proteinuria accounted for less than 25% of the total metabolism. The survival times of lambda- and kappa-type human Bence Jones proteins and the Bence Jones protein produced by mice with MPC-2 plasma cell tumor were exceedingly short in both unoperated and ureter-severed mice, with 50% of the injected protein catabolized in from 0.8-1.6 hr. In contrast, the survival of Bence Jones protein was markedly prolonged in nephrectomized animals, with 50% of the injected dose catabolized in from 9 to 17 hr. This ten-fold decrease in catabolic rate indicates that the kidneys are the major site of breakdown of Bence Jones proteins. Similar studies with other proteins indicated that the kidneys are also the major site for catabolism of isolated L chains but not of intact IgG molecules. The Fc immunoglobulin fragment was not catabolized and the Fab fragment only partially catabolized by the kidney. When ureter-severed animals were allowed to develop advanced uremia before being studied, the survival of Bence Jones protein was greatly prolonged, indicating that the catabolic process is impaired in the presence of uremia. The nature of this renal catabolism remains unknown. These observations suggest that the Bence Jones proteins and L chains observed in the urine of patients may reflect only a small fraction of such molecules synthesized by these patients. Furthermore, they provide an explanation for the prolongation of Bence Jones protein survival and the development of Bence Jones proteinemia observed in subjects with multiple myeloma and impaired renal function.

CLINICAL INDICATIONS FOR KIDNEY SCANNING.

Kidney scanning with radioactive mercury compounds is a diagnostic procedure which should be used more than it is at present. No patient preparation or instrumentation is necessary. Patient sensitivity to mercury has not been encountered. There is no interference from gas and fecal matter. Sharp contrast between functioning and nonfunctioning areas, definition of functioning renal mass, and tissue visualization in the presence of azotemia are obtained. These advantages outweigh the problems of isotope handling, instrument technicalities, special training, and minimal limitations in interpretation. Among the indications for mercury kidney scanning are iodine allergy, inadequate roentgenography, and a need for spatial and functional evaluation.

Digitalis tolerance and effect of acetyl-strophanthidin upon serum potassium of dogs with acidosis and uremia

Evidence exists that the cardiac glycosides may initiate important shifts in the concentration of potassium (K) in both cellular and extracellular fluid.l-4 Their administration to normal dogs usually produces slight increases in serum K.1 Two clinical observations have also suggested a peculiarity of action of this drug in the uremic state. First, digitalization of patients with renal insufficiency sometimes apparently causes serum K to rise significantly, and second, some uremic patients have become intoxicated with relatively modest amounts of digitalis. In an attempt to evaluate these clinical impressions the effects of acetyl-strophanthidin (AS) upon the electrocardiogram and the serum electrolyte pattern of normal dogs were compared with those occurring in dogs made acidotic with ammonium chloride or uremic by bilateral ureteral ligation. Changes in tolerance to AS were also studied in each group. The results suggest that digitalis may induce significant hyperkalemia in the presence of uremia or metabolic acidosis. The results may be explained on the basis of previously reported alterations in permeability of the cell membrane.

The prognostic significance of the blood urea nitrogen following hematemesis or melena

The blood urea nitrogen was elevated to 30 mg. per cent or more in about two-thirds and to 50 mg. per cent or more in about one-fifth of one hundred and thirty-five cases of hematemesis or melena due to various causes. In no instance of hematemesis due to peptic ulcer, hepatic cirrhosis, gastritis, carcinoma, or undetermined cause, did death occur as the result of the hemorrhage in the absence of an increased blood urea nitrogen content. In the presence of azotemia five of eight patients with hepatic cirrhosis died as did seven among thirty-five patients with peptic ulcer (including one patient who died of perforation). In the presence of azotemia shock increased the mortality rate in patients with hematemesis or melena. The mean maximum blood urea nitrogen was higher in patients fifty years of age or over than in those below this age limit. In patients with repeated or continued hemorrhages which proved fatal the already elevated blood urea nitrogen generally continued to rise or fluctuated above normal limits instead of reaching a maximum concentration in twenty-four to forty-eight hours and then dropping to normal on the third or fourth day as in patients with a single non-fatal hemorrhage.